Apitope Announces Positive Results with Novel Treatment for Graves' Disease

HASSELT, Belgium and CHEPSTOW, Wales, April 16, 2018 /PRNewswire/ --

Phase I data show early efficacy in the majority of patients and a very favourable safety profile

Apitope, a clinical stage biotech company developing potential first-in-class antigen-specific immunotherapies targeting autoimmune diseases (including multiple sclerosis (MS), Graves' disease and uveitis), today announced positive results from the Phase I first in man clinical trial of its product candidate, ATX-GD-59, in development for the treatment of Graves' disease.

Graves' disease is one of the most common autoimmune diseases with approximately 10 million patients across Europe and the US and yet there have been no innovative treatments in more than 60 years. With Graves' disease, the immune system mistakenly attacks the thyroid gland and causes it to become overactive. Symptoms can include an enlargement of the thyroid gland, swelling of the neck, localised abnormalities of skin, tremors, heat intolerance and sweating, significant weight loss, osteoporosis, atrial fibrillation and ocular changes in patients. Each year 20-30 out of every 100,000 people are newly diagnosed with Graves' disease. The ratio of women versus men diagnosed with Graves' disease is 6:1 and around 2% of all women will develop Graves' disease during their lifetime.

Dr Simon Pearce, Professor of Endocrinology, Newcastle University, and Chief Investigator for the trial commenting on the results said: "It is very exciting to see these promising Phase I results where ATX-GD-59 has shown both an encouraging safety and tolerability profile as well as efficacy. With current first-line treatments having a high failure rate, and the second-line treatments being either invasive surgery or radioiodine, ATX-GD-59 demonstrates the potential to address the high medical need for a new, safe and effective treatment for the neglected field of those suffering from Graves' disease."

The Phase I clinical study met the primary endpoint to assess the safety and tolerability of ATX-GD-59 in 12 patients with Graves' disease. The majority of the per protocol subjects were either euthyroid, the clinical objective of therapy, or close to being euthyroid by the end of treatment; the effect was maintained during the 3 months follow up off therapy. Importantly, TSHR antibody levels were also reduced with close correlations between percentage decreases in antibody and thyroid hormone levels in line with the mechanism of action.

Dr Keith Martin, Chief Executive Officer of Apitope, commented: "We're highly encouraged by these data as they provide further evidence that our Apitope® platform identifies safe and effective treatments for autoimmune diseases. These findings are important for Graves' disease patients in providing a potential new treatment paradigm aimed at the cause of the disease not just the symptoms. We will continue to progress the development of ATX-GD-59 as a treatment for Graves' disease and are currently preparing to initiate a Phase II study in the first quarter of 2019."

The investigational product was administered intradermally (ID) every two weeks over a period of 18 weeks in male and female patients that were not otherwise being treated with anti-thyroid therapy. Following a titration period of 25, 50, 100, 400 and 800 μg in the initial eight weeks of treatment, a dose of 800 μg was administered fortnightly for an additional 10 weeks, comparable to the regime followed in the successful ATX-MS-1467 multiple sclerosis (MS) trials.

About Apitope  

Apitope is a clinical stage biotech company that develops potential first-in-class antigen-specific immunotherapies targeting autoimmune diseases.

Apitope uses its novel, proprietary discovery platform to select and develop highly specific peptide-based therapeutics, known as "apitopes®" (antigen processing independent epitopes), that directly target the immunological basis of autoimmune diseases, including multiple sclerosis (MS), Graves' disease and uveitis, as well as undesired immune responses against biologic therapeutics used in the treatment of life-threatening disorders such as haemophilia A.  

While current therapies for autoimmune diseases typically have the effect of suppressing the immune system, apitopes® modulate only the malfunctioning part of the immune system in order to avoid such global immune suppression. The apitope® mechanism of action and platform have the broad potential to treat a wide variety of autoimmune diseases. Apitope has a robust pipeline of innovative, potential first-in-class product candidates in clinical and pre-clinical development. Apitope's lead product candidate ATX-MS-1467 is in development for the treatment of MS, and is ready to start a Phase IIb clinical trial.

Apitope was founded in 2002 by Professor David Wraith, as a spin-out from the University of Bristol. It is based in Diepenbeek, Belgium, which is home to Apitope's research and finance activities, and Chepstow, United Kingdom, where Apitope's development and commercialisation activities are located. For more information please visit: https://apitope.com/

Autoimmune diseases 

An autoimmune disease occurs when the immune system mounts an undesired response to an innocuous self-antigen and attacks healthy tissues in the body. Autoimmune diseases are typically treated with therapies that globally suppress the immune system. Such therapies address the symptoms of the disease, not the cause, and increase the risk to life-threatening infections, cancers and other immune complications.

There are at least 80 types of autoimmune diseases^[1] including MS, Graves' disease, and uveitis. Up to 50 million people are suffering from autoimmune disease in the U.S. alone^[2], where it is one of the leading causes of death in women in all age groups up to 65^[3].

Treatments for autoimmune diseases represent a large and active industry that has been gaining momentum, with five out of ten best selling drugs in 2016 targeting autoimmune diseases^[4].

Graves' disease 

Graves' disease is an autoimmune disease in which the immune system mistakenly attacks the thyroid gland and causes it to become overactive. It is characterized by an immune response against the extracellular domain of the thyroid stimulating hormone receptor (TSHR) on the thyroid gland resulting in pathological increases in thyroid hormone levels. Symptoms of Graves' disease can include an enlargement of the thyroid gland, swelling of the neck, localised abnormalities of skin, tremors, a decreased heat or cold tolerance, significant weight loss, osteoporosis, atrial fibrillation causing embolic events and tachycardia, and ocular changes that result in the appearance of a wild or staring expression in patients where the disease extends to affect the eyes. Graves' disease is one of the most common autoimmune diseases, with approximately 10 million Graves' disease patients across Europe and the U.S., and 20-30 out of every 100,000 people are newly diagnosed with Graves' disease each year. Around 2% of women will develop Graves' disease during their lifetime and the ratio of women versus men diagnosed with Graves' disease is 6:1.

^[1] Office of Women’s Health US

^[2] American Autoimmune Related Diseases Association

^[3] American Journal of Public Health. 90 (9): 1463-6 4. N Engl J Med. Sep 2002 347(12):911-920

^[4] Speights, K. (2017). The 9 Best Selling Prescription Drugs in 2016